Your Digest for Sunday, Jan 21, 2024 08:59 AM


Variation of thyroxine in pregnancy

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Some definitions

In parasitology, a definitive host is an organism that harbors a parasite that has reached sexual maturity. An intermediate host is an organism that harbors a parasite that has not yet reached sexual maturity. - Bard

Trypanosomiasis - sleeping sickness

#insect-vector #lymphadenopathy
Pathogen : protozoan - trypanosoma sp.
Vector : Tsetse fly - Glossina
Enedemic to subsaharan africa
About a week after the bite, the patient develops a chancre at the site of the bite.
Other syptoms are lymphadenopathy (painless, posterior chain) and hepatosplenomegaly.
The parasite moves through the lympathic system can can invade the CNS --> late stage symptoms involve CNS dysfunction (aka. sleeping sickness)
Usually a slowly progressing disease; many are diagnosed incidentally.

Treatment: nifurtimox-eflornithine, fexinidazole, pentamidine
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Legionella pneumonia

Levofloxacin and azithromycin are the preferred agents for the treatment of Legionnaires' disease because these agents are bactericidal, achieve high intracellular concentrations, penetrate lung tissue, and are active against all Legionella species that cause human infection. Alternatives include other fluoroquinolones (eg, moxifloxacin, ciprofloxacin) and other [[Antibiotics#Why clarithromycin? Why is it interchangeable with metronidazole|macrolides]] (eg, clarithromycin, roxithromycin)

[!TIP] Mycoplasma causes immune phenomena
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Mycoplasma pneumonia

Mycoplasma is one of the smallest known free living organisms.
No cells wall -> beta lactams won't work.

Commonest manifestation is upper respiratory tract infection.
but mycoplasma pneumonia is a common cause of community acquired pneumonia as well.
Most mycoplasma associated URTI and LRTI are mild and self limiting; They may not even need ABx. Pursuing a microbiological diagnosis usually isn't necessary as management won't change.

Clinically and radiologically, mycoplasma pneumonia has no distinguishing features from other atypical pneumonia except

CXR - uni / bi lateral reticulonodular patchy opacities. ( Looks almost normal)
Direct Coombs test and cold-agglutinin titers are typically positive

Diagnosis: PCR
?FBC results - WBC mildly elevated

Directed treatment of M. pneumonia − For patients with microbiologically confirmed M. pneumoniae pneumonia, first-line treatment options include macrolides (eg, azithromycin), tetracyclines (eg, doxycycline), and respiratory fluoroquinolones (eg, levofloxacin or moxifloxacin).

Cholera

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Agent: Vibrio cholerae - flagellated gram -ve bacteria. (flagella allows it to swim through mucous and reach the epithelium) (O1 and and O139 are the only ones that have caused epidemics)
Symptoms: Infection can be mild but massive "rice water" diarrhoea is the main clinical feature. 50-70% mortality if untreated. Median time to death from symptom onset is a little as 12 hours.

Cholera toxin has A and B subunits. B subunit facillitates toxin entry. A subunit promotes chloride secretion and inhibits sodium chloride resorption ==> Result is profuse water diarrhoea.
Incubation period is around 2 days but can even be hours (Short!)

Stool of patients contains high amounts of Na, K and HCO3.

Diagnosis is by culture of stool on selective media. (peptone alkaline media etc. ) Clinical diagnosis is usually possible.
Complications: Hypo/ hypernatremia, hypokalemia, met. acidosis, hypocalcemia and cramps,
Management : Aggressive fluid replenishment.
Antibiotics shorten disease duration : macrolides, fluoroquinolones and tetracyclines.
Oral killed vaccines and { live attenuated vaccines (for travellers) } is available.
[[2022 May Basic Sciences#Cholera vaccine|Cholera vaccine]]

📑Typhoid

[!INFO] Introduction to salmonella
Salmonellae are motile gram-negative bacilli that infect or colonize a wide range of mammalian hosts.
Salmonellae cause a number of clinical infections in humans; these include:

#2023GM Q32

📑Enteric fever

[!TIP] Fever + abdominal pain + GI symptoms
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Look for specific signs - relative bradycardia, temperature pulse dissociation, rose spots ==> Enteric / Thyphoid fever.

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📑Causative agent: Salmonella typhi AND S. Paratyphi A B and S
📑Humans are the only host of these.😔

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Infection can result in

  1. Acute illness
    Symptoms: "stepwise" fever + chills + abdominal pain 📑5-21 days after exposure. (Not rapid like cholera )
    GI symptoms: diarrhoea or constipation + abdominal pain.
    Other signs: relative bradycardia, pulse-temperature dissociation, and "rose spots".
    Rose spots are ❗non tender, blanching papules. - occurs in 2nd week.
    Intestinal rupture (3rd week) -> ? sepsis
    #splenomegaly during 3rd week
    typhoid encephalopathy in severe disease.

  2. Chronic carrier state - minority of cases only.

    1. Chronic Salmonella carriage is defined as excretion of the organism in stool or urine >12 months after acute infection
    2. Commoner in females and those with biliary problems like cholelithiasis.

Investigations:

Diagnosis: Culture of organism from blood, stool, bone marrow, urine or rose spots / ELISA

Treatment: Antibiotics :

Prevention: two types of 📑vaccinations are given : live attenuated (oral) and antigen based (IM)

👌🏼Nontyphoidal salmonella

#2019BSQ-OCT/33
(search Non-typhoidal salmonella)

Malaria

Comparison of malaria species

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url.pngSource

[!TIP] Falciparum = F*cked
Infects RBC of all ages, end organ damage and death is common and parasitaemia can be very high!
Worldwide , highest mortality is from Falciparum.

[!TIP] Only organisms containing V in their name have LIVER stages.

P Falciparum => No relapses from liver! FALCIPARUM DOES NOT FORM HYPNOZOITES!
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P vivax => relapsing illness, less severe than falciparum. But still can cause end organ damage and death.
P Ovale => Relapsing illness but less severe than vivax
P malariae => Chronic low level parasitaemia and anaemia; resultant chronic anaemia can cause significant morbidity

Malaria red cell entry receptors:

Plasmodium falciparum invades human erythrocytes by redundant pathways.
Unlike P. vivax that has one Duffy Binding-Like (DBL) receptor, P. falciparum has four members of the DBL receptor family.

Malaria life cycle

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"sporos" meaning "seed" or "spore," and "zoion" meaning "animal" or "living being."
"merozoite" - "Meros" means "part" or "segment," while "zoion" translates to "animal"
trophē," meaning "nourishment" or "food," and "zoion," meaning "animal"; During the trophozoite stage, the parasite actively feeds on host cells or ingested materials, acquiring the necessary nutrients for growth and reproduction

The life cycles of P. vivax and P. ovale include a dormant hepatic stage called the hypnozoite.
Relapse shows same symptoms as primary infection; can occurs in weeks, months or years
Dormant hypnozoites don't cause symptoms can cannot be detected by any tests

Vivax and ovale infect reticulocytes.

In P Ovale, all stages of the life cycle are seen in the blood film whereas in P. falciparum only trophozoites and gametocytes are seen in the blood. (therefore, if all forms are seen, chloroquine can be given. )
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Bone marrow infection:

[!TIP] The two organisms causing the most severe forms of disease infect bone marrow.

Malaria clinical features

falciparum malaria Non falciparum malaria
Most will have daily spiking fever
Falciparum, vivax and ovale have tertian fever spikes (48 hourly) Clinical features are fever, N/V,cough, ArA, MyA, headache, malaise etc.

High fevers with delirium

Febrile paroxysms may occur every other day for P. vivax, P. ovale, and P. falciparum and every third day for P.malariae. Paroxysms occurring at regular intervals are more common in the setting of infection due to P. vivax or P. ovale than P. falciparum

Pathogenesis of disease in malaria infection

All species of plasmodium adhere to cell surfaces in humans. In P falciparum, the time of adhesion is a significant portion of the life cycle.

Falciparum infection of RBC -> RBC produces sticky knobs of proteins -> RBC adhere to capillary endothelium -> sequestration -> partial blood flow obstruction -> complications like cerebral malaria and renal failure.

Diagnosis of malaria

Thick and thin films are used for rapid diagnosis. Thick Vs. Thin film preparation

Thick Film Thin Film
Red cells lysed Red cells preserved
Can see parasite inside cell; good to identify parasite species
larger number of cells per field : good for screening and estimating parasite density Can accurately calculate parasite density

Films should be repeated every 8 - 12 hours if malaria is suspected.

Parasitaemia (usually < 0.1% of red cells are infested)
Severe paracitaemia = > 5% of cells area affected.
Other Lab Ix:
Severe Anemia (massive intravascular haemolysis), thrombocytopenia,
Elevated transaminases,
mild coagulopathy
elevated blood urea nitrogen (BUN) and creatinine

Chronic malaria can cause Hyper-reactive splenomagaly - aka tropical splenomegaly syndrome. Chronic production of IgM -> immune complexes -> stimulation of RET system -> #splenomegaly

Severe Malaria

Severe malaria can occur with any species but patients with severe malaria should be managed as having falciparum.
Severe malaria occurs when there is organ failure; (defined as any one of the following in presence of malaria infection and after excluding other causes)

Many of the clinical findings are the result of the parasitized RBCs adhering to the endothelial cells lining small blood vessels ("cytoadherence") causing small infarcts, capillary leakage, and organ dysfunction

Treatment for severe malaria is IV or IM Artesunate

Blackwater fever is a rare complication of malaria which can be fatal. It is caused by large intravascular haemolysis resulting in haemoglobinuria, anaemia, jaundice and acute kidney injury. Urine is classically black or dark red in colour.The cause of the massive haemolysis is unknown. The treatment is with antimalarials, intravenous fluids and in some cases dialysis. Urinalysis reveals blood which is not seen on microscopy as it is haemoglobinuria.

Treatment of malaria

[!INFO] Summary

Falciparum and vivax both have high prevalence of chloloquine resistance!

For falciparum, ACT (artemisinin based combination therapy) is the first line drug.
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ACT = artemether + lumefantrine (one of several drug combinations grouped under ACTs). All combinations are equally effective. (If body weight > 65 Kg, artemisinin + lumifantrine may be less effective)

Artemisinins should be administered with a second agent that has a longer half-life than the artemisinin drug to forestall development of artemisinin resistance and to provide an extended duration of drug level to clear parasitemia
Using artemisinins alone would lead to treatment failure.

If ACT is unavailable and if local falciparum is sensitive to chloroquine-> then chloroquine can be used.
Treatment duration is 3 days. Artemisinin resistance is identified if parasite levels are > 100,000 / microL on day 3. If so, treatment duration is extended to 6 days.
South asian P. Vivax is resistant to chloroquine (?sensitive in other regions) -> Give ACT for vivax infections.

Quinine based regiments can be used as alternatives if ACT resistance is prevalent. Consists of quinine + (doxycycline / tetracyclin / clindamycin). ACT is preferred over quinine regiments because quinine regimens can cause reversible tinitus and high tone hearing loss + GI side effects.

Primaquine reduces transmisibility. Main action is to eradicate hyponozoites. Also acts against gametocytes but has no effect against asexual blood stages.
(i.e so it works against hypnozoites and gametocytes)
Primaquine is contraindicated in #pregnancy and children < 6 months old. Primaquine can cause haemolysis in [[Anaemia#G6PD deficiency|G6PD deficiency]].

Mefloquine - given for prophylaxis - can cause acute psychosis if toxicity occurs. Can be used in pregnancy.
Chloroquine and mefloquine are unsuitable as chemoprophylaxis in patients with epilepsy!

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Treatment of malaria in #pregnancy

ACT is safe in pregnancy
Chloloquine is safe in pregnancy.
artesunate is safe in any trimester.
Primaquine is problematic because it exacerbates G6PD-deficiency anaemia;

Prophylaxis against malaria infection

#2020GM-NOV/Q43

Dengue fever

Dengue has an incubation period of about 1 week (3-14 days) so travellers can develop fever about 1 week after returning
flavivirus
Aedes aegypti - day biter
lymphadenopathy can occur. - ?rare

Clinical features of Dengue

A rash (generalized, macular / maculopapular, blanching, pruritic) can occur in the acute phase of dengue as well. (not just the convalescent phase)
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Yellow fever

Hepatitis A

Self limited.
Few progress to fulminant hepatic failure -> poor prognosis.

Measles

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Two phases :
Phase 1 : catarrhal phase : rhinorrhoea, cough, conjunctivitis, koplik's spots in the oral mucosa (lasts 2 - 4 days)
Phase 2: Eruptive / exanthematous stage : rash that spreads form the head outward. (fades away in the same order) (occurs 2 - 4 days after onset of fever)
infective 4 days before and 2 days after onset of rash.
Incubation period 8-14 days.
Droplet spread; highly infective.
No foetal abnormalities.
#2021BSQ-NOV/Q37
Subacute sclerosing panencephalitis (symptoms occur due to viral reactivation in teenage years) and post measles encephalomyeltis (2 weeks after infection) are dreaded complications.

Cyclospora cayatensis infection

Protozoan
Obligate human parasite (Humans are only known host)
Ingestion of sporulated oocyst from fruits / vegetables / water -> infection -> infection of GI mucosa
Low grade fever with anorexia, nausea, flatus, diarrhoea (symptoms can be chronic)
Direct faeco oral transmission is not possible as defecated unsporulated oocyst must mature for days / weeks in the environment.
Treatment: trimethoprim sulfamethoxazole.

Schistosoma

[!TIP] Patient goes swimming in fresh water and then presents with haematuria or diarrhoea. NOT A gastrointestinally acquired pathogen.

[!INFO] AKA Bilharziasis
after the name of the disoverer

schistosomaFreshWater.png

[!TIP] Mnemonic for the species:

Treatment: Praziquantel - antihelminthic drug and steroids to reduce inflammation.

Leishmaniasis

#2020BSQ-NOV/Q67
#2020BSQ-JUL/Q41

[!WARNING] Leishmaniasis is a notifiable disease in Sri Lanka as of 2008

Leishmaniasis causes suppurative granulomas

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Leishmaniasis in Sri Lanka

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[!TIP] Leishmaniasis in Sri Lanka
DCOSL -> Donovani, cutaneous, in Sri Lanka
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Source

In SL, leishmaniasis is reported mainly in Anuradphapura, polonnaruwa, hambantota and Matara. The disease was began spreading locally in the 1990s. Incidence has been increasing rapidly in the past decade.

Sri lanka is endemic for Leishmaniasis caused by Leishmania donovani.

In Sri Lanka, Leishmania donovani (usually associated with visceral leshmaniasis (VL)) causes cutaneous leishmaniasis (CL). This is termed dermotropism. However, it can cause VL as well.
Phelbotomus argentipes is the main vector in SL although others are also present.
In SL, Leishmania incidence is seasonal.

Leishmaniasis has a wide spectrum of disease.

Cutaneous leishmaniasis

Protozoan parasite.
Many species; each one having somewhat different clinical picture.

Diffuse cutaneous

Diffuse cutaneous leishmaniasis — is a rare syndrome that occurs mainly in the setting of L.L. aethiopica, L.L. mexicana, and L.L. amazonensis infection.
It begins as a localized lesion that does not ulcerate; rather, amastigotes disseminate to macrophages in other areas of the skin. People who develop DCL usually have a defect in cell mediated immunity.

Musocal leishmaniasis

Visceral leishmaniasis

aka Kala-azar (Hindi: black fever)

Post kala-azar dermal leishmaniasis (PKDL)

Bubonic plague

Yersinia pestis.
Transmitted by bite of rodent associated flea.
Fever, headache, chills, and weakness and one or more swollen, painful lymph nodes (called buboes).
Can be fatal without antibiotics.

Rocky mountain spotted fever

Tick borne disease which can be fatal if untreated.
Ricketsia rickettsii - gram negative obligate intracellular pathogen; infects vascular endothelial cells; causes vasculitis and increased capillary permeability.

Q fever: Coxiella burnetti

#2020BSQ-JUL/Q54
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Zoonosis; Obligate intracellular parasite. commonest reservoir is goats, cattle, cats.
Infective fluids come from anogenital systems : faeces, urine, birth products and milk.
Infection is by inhalation of aerosols. Infectious dose is very small to minimal contact can cause infection.

Pincu is a 2 - 4 weeks.
Infection can cause:

Enterococcus infection

#2020GM-NOV/Q14